The bovine foot skin microbiota is associated with host genotype and the development of infectious digital dermatitis lesions.

BACKGROUND: Bovine Digital Dermatitis (BDD) is a prevalent infectious disease, causing painful foot skin lesions and lameness in cattle. We describe herein the bovine foot skin microbiota and its associations with BDD using 16S rRNA gene amplicon and shotgun metagenomic sequencing on samples from 259 dairy cows from three UK dairy farms. RESULTS: We show evidence of dysbiosis, and differences in taxonomy and functional profiles in the bovine foot skin microbiome of clinically healthy animals that subsequently develop BDD lesions, compared to those that do not. Our results suggest that taxonomical and functional differences together with alterations in ecological interactions between bacteria in the normal foot skin microbiome may predispose an animal to develop BDD lesions. Using genome-wide association and regional heritability mapping approaches, we provide first evidence for interactions between host genotype and certain members of the foot skin microbiota. We show the existence of significant genetic variation in the relative abundance of Treponema spp. and Peptoclostridium spp. and identify regions in the bovine genome that explain a significant proportion of this variation. CONCLUSIONS: Collectively this work shows early changes in taxonomic and functional profiles of the bovine foot-skin microbiota in clinically healthy animals which are associated with subsequent development of BDD and could be relevant to prevention of disease. The description of host genetic control of members of the foot skin microbiota, combined with the association of the latter with BDD development offer new insights into a complex relationship that can be exploited in selective breeding programmes. Video Abstract.

16S rRNA amplicon sequencing reveals a polymicrobial nature of complicated claw horn disruption lesions and interdigital phlegmon in dairy cattle.

Lameness represents an intractable problem for the dairy industry. Complicated claw horn disruption lesions, interdigital hyperplasia, and interdigital phlegmon are important lameness causing foot lesions. Their aetiology is multifactorial, but infectious processes are likely implicated in disease pathogenesis. Our aim was to investigate the bacterial profiles of these lesions using 16S rRNA gene sequencing of samples obtained from 51 cattle across ten farms in the UK. In this study, interdigital hyperplasia, interdigital hyperplasia with signs of interdigital dermatitis, interdigital phlegmon, complicated sole ulcers, complicated toe ulcers lesions, and complicated white line lesions were investigated; corresponding healthy skin control samples were also analysed. All diseased tissues displayed reduced microbial richness and diversity (as described by Chao1, Shannon, and Simpson alpha-diversity indices) compared to their healthy skin control samples. Our results confirm the association of Treponema spp with some of these disorders. Other anaerobic bacteria including Fusobacterium spp., Fastidiosipila spp. and Porphyromonas spp. were implicated in the aetiology of all these lesions with the exception of interdigital hyperplasia. Complicated claw horn disruption lesions, and interdigital phlegmon were found to have similar bacterial profiles. Such sharing of bacterial genera suggests many of the infectious agents detected in these foot lesions are acting opportunistically; this finding could contribute towards future treatment and control strategies.

Surface-confined [2 + 2] cycloaddition towards one-dimensional polymers featuring cyclobutadiene units.

Surface-confined synthesis has been offering a wide range of opportunities for the construction of novel molecular nanostructures. Exploring new types of on-surface coupling reactions is considered essential for being able to deliberately tune the materials properties. Here, we report on the formation of a covalent C-C bonding motif, namely 1,3-cyclobutadiene, via surface-confined [2 + 2] cycloaddition between pyrene moieties using low temperature scanning tunneling microscopy (LT-STM) and X-ray photoemission spectroscopy (XPS) measurements. By employing a hydrogen dosing treatment together with low-temperature activation, we were able to both eliminate residual byproducts and obtain covalent 1D polymers through the formation of 1,3-cyclobutadiene units. The resulting C-C bonding motif has so far hardly been explored in surface chemistry and substantial evidence is provided that the hydrogen treatment is crucial towards the removal of byproducts in surface-confined polymerization.

On-Surface Formation of Cumulene by Dehalogenative Homocoupling of Alkenyl gem-Dibromides.

The on-surface activation of carbon-halogen groups is an efficient route to produce radicals for constructing various hydrocarbons and carbon nanostructures. To date, the employed halide precursors have only one halogen attached to a carbon atom. It is thus of interest to study the effect of attaching more than one halogen atom to a carbon atom with the aim of producing multiple unpaired electrons. By introducing an alkenyl gem-dibromide, cumulene products were fabricated on a Au(111) surface by dehalogenative homocoupling reactions. The reaction products and pathways were unambiguously characterized by a combination of high-resolution scanning tunneling microscopy and non-contact atomic force microscopy measurements together with density functional calculations. This study further supplements the database of on-surface synthesis strategies and provides a facile manner for incorporation of more complicated carbon scaffolds into surface nanostructures.

Chiral-Selective Formation of 1D Polymers Based on Ullmann-Type Coupling: The Role of the Metallic Substrate.

The chiral-selective formation of 1D polymers from a prochiral molecule, namely, 6,12-dibromochrysene in dependence of the type of metal surface is demonstrated by a combined scanning tunneling microscopy and density functional theory study. Deposition of the chosen molecule on Au(111) held at room temperature leads to the formation of a 2D porous molecular network. Upon annealing at 200 °C, an achiral covalently linked polymer is formed on Au(111). On the other hand, a chiral Cu-coordinated polymer is spontaneously formed upon deposition of the molecules on Cu(111) held at room temperature. Importantly, it is found that the chiral-selectivity determines the possibility of obtaining graphene nanoribbons (GNRs). On Au(111), upon annealing at 350 °C or higher cyclo-dehydrogenation occurs transforming the achiral polymer into a GNR. In contrast, the chiral coordination polymer on Cu(111) cannot be converted into a GNR.

[Struma with euthyroidism ]. / Struma mit Euthyreose.

A total of 75-85% of thyroid operations are performed on euthyroid goiters; 70% of them are bilateral. Ultrasonography is the most important preoperatively examination. But even lobes classified as normal should be inspected carefully during operations: nodules were found in so called "normal" lobes in 22%. All nodules have to be resected, and attention must be paid to retrosternal and retrovisceral parts. Identification of recurrent nerves and parathyroid glands is necessary. Recurrent goiters should be prepared intercapsularly. In our own 3049 cases of euthyroid goiters 2.4% had early recurrent nerve paralysis, 3.9% retrosternal and 6.6% recurrent goiters.

Diffuse sclerosing variant of papillary thyroid carcinoma. S-100 protein immunocytochemistry and prognosis.

The recently published second edition of the WHO classification of thyroid tumours describes the diffuse sclerosing papillary carcinoma (DSPC) as a specific variant of papillary thyroid cancer (PC). Besides several histological hallmarks, this rare tumour is characterized by its occurrence in young individuals and is thought to have a less favourable prognosis than PC in general. The observations on two examples of this tumour presented herein, however, are at variance at this assumption. The neoplasms occurred in a 10 year old girl and a 34 year old woman. Each time, diffuse involvement of both thyroid lobes and bilateral cervical lymphadenopathy were seen. In one case, the carcinoma extended into the cervical soft tissue. Follow-up disclosed both patients to be without evidence of disease 2 and 13 years, respectively, after thyroid surgery. Immunocytochemically, both thyroid primaries as well as 7 other cases of DSPC reported in the literature showed dense accumulations of S-100 protein positive dendritic/Langerhans cells. Such infiltrations have been demonstrated to be correlated with a benign clinical course of PC. It is thus suggested that DSPC behaves similarly or even less aggressively than PC in general, at least if prominent Langerhans cell infiltration is present.

[Identification of the recurrent laryngeal nerve in thyroid gland surgery--a status determination]. / Darstellung des Nervus recurrens bei Schilddrüsenoperationen--Standortbestimmung.

The recurrent laryngeal nerve palsy is the most important complication in thyroid surgery. It seems to be possible to reduce the rate of palsies by consequently identifying the recurrent laryngeal nerve. A comparison of statistics out of the literature with and without identification of the recurrent laryngeal nerve shows this. A follow-up of our patients of the years 1980-1982 (1312 operations) confirms this finding.

[Immunohistology and prognosis in thyroid cancer. Determination of the malignancy potential of papillary and medullary neoplasms by the detection of S-100 protein and Leu-M1 antigen]. / Immunhistologie und Prognose beim Schilddrüsenkarzinom. Bestimmung des Malignitätspotentials papillärer und medullärer Neoplasien durch S-100-Protein- und Leu-M1-Antigen-Nachweis.

170 thyroid carcinomas were investigated for the presence of S-100-protein-positive Langerhans cells (LC) and the expression of Leu-M1-antigen. Dense LC infiltrates were found only in papillary tumours and were shown to be significantly related to prognosis. Irrespective of any other feature, no single instance of death resulting from cancer occurred among 23 tumours (including 6 cases of stage pT4) with dense infiltrates (greater than 20 LC/unit field) while 9/53 (17%) of the remaining patients died from carcinoma (p less than 0.01). The degree of epithelial Leu-M1 expression was significantly related to the biological behaviour of papillary and medullary neoplasms. Death resulting from cancer occurred 17 times more frequently among papillary tumours with marked positivity (greater than 15%) as compared to cases with slight or absent immunoreactivity (8/24 vs. 1/52; p less than 0.00005). Among medullary carcinomas, local recurrences occurred 2.9 times (14/16 vs. 7/23; p less than 0.005) and death resulting from tumour occurred 4.3 times (9/16 vs. 3/23; p less than 0.03) more frequently for intensely stained as compared to slightly immunoreactive and unstained neoplasms.

[Perforation of gastroduodenal ulcer. Risk factors and choice of procedure]. / Perforation des gastroduodenalen Ulkus. Risikofaktoren und Verfahrenswahl.

The well known surgical risk factors, such as age, time of perforation as well as size and localisation of necrosis, were confirmed in retrospective and prospective analyses of perforation of gastroduodenal ulcers (n = 504). Incidence was unchanged in the two different time-related groups, with 3.2 or 3.7 cases in one month. There was a clear-cut need for excision of the ulcer or necrotic margin. Perforation was attributable to malignant tumours in 2.1 per cent of the cases. The authors have definitely adopted the concept of earlier primary surgery (23 per cent of all cases, as compared to 10.4 per cent before). The risk associated to it was found to be lower than linked to palliative operations. The lethality rate was as low as 7.6 per cent, once due consideration was given to the above risk factors for adequate choice of surgical methods. Particular attention was given to ulcer localisation and clinical course. Hence, lethality has clearly dropped below earlier data.

[Technics and complications in reinterventions on the thyroid]. / Technik und Komplikationen bei Rezidiveingriffen an der Schilddrüse.

In preference to the two long-established operative procedures for recurrent goitre - extracapsular and intracapsular resection - we have introduced meticulous preparation between the thin capsule around the recurrent goitre and the more solid external capsule in a procedure which combines the advantages of both older methods and avoids most of their pitfalls. The recurrent laryngeal nerves and the parathyroids are always outside the external capsule. The incidence of injury to these structures is minimised by this procedure. From 1980-1985 we performed 2575 thyroid operations, of which 165 operations were for recurrent goitre (6.4%), bilateral in 89 cases. Two patients died of cardiopulmonary complications (1.2%). Preoperative laryngeal nerve palsy was present in 21 cases, postoperative acquired nerve injuries occurred in 28 patients, all in all 31 nerve paralysis (18.8%), or 12.2% when compared with nerves at risk. Eight patients suffered laryngeal nerve palsy on both sides (five with preoperative nerve palsy on one side). Eleven patients showed normal function of laryngeal nerves on follow-up, whilst permanent nerve palsy was found in seventeen cases (10.3%), or 6.7% when related to nerves at risk. Hypoparathyroidism was found in 7 patients of which 4 cases showed permanent changes (2.4%).

Autoradiographical evidence for increased thyrotropin binding to autonomously functioning thyroid gland tissue.

The aim of this study was to quantify thyrotropin (TSH) binding to individual cells from autonomously functioning thyroid gland tissue (AFTT) in comparison with the corresponding non-autonomous cells. Cryostatic tissue sections from ten thyroid glands with autonomously functioning adenomas were incubated in 125I-labeled TSH. TSH-binding density (TBD) was visualized by means of autoradiography and quantified by means of reflection photometry. Eight out of ten specimens showed a significant (p less than 0.001), up to tenfold increase in TBD of AFTT cells. All ten specimens had a significantly increased number of TSH molecules bound per thyrocyte in comparison both with the corresponding non-autonomous cells and also with tissues from non-functioning thyroid neoplasms (n = 6). The increased TBD of AFTT persisted after transplantation onto nude mice. The paranodular tissue from thyroid glands with scintigraphically compensated adenomas showed in four out of six cases an increased TBD when compared with normal thyroid tissue. It can be concluded that AFTT possesses distinct cytoplasm membrane characteristics as evinced by TSH binding analysis. Increased TSH binding should be considered as a possible cause of metabolic hyperactivity of AFTT cells. The concomitant existence of functional autonomy in the paranodular tissue might lead to a false supposition of a compensated autonomous adenoma as revealed by scintigraphical evidence.

Leu-M1 immunoreactivity and prognosis in medullary carcinomas of the thyroid gland.

Leu-M1 antigen is a monocyte/granulocyte-related marker known to be consistently expressed in the Reed-Sternberg cells of patients with Hodgkin's disease and to be present in tumour cells of a variety of non-haematopoietic neoplasms, most of them adenocarcinomas. The biological significance of this aberrant reaction has not yet been clarified. Recently, however, we have demonstrated that marked epithelial Leu-M1 immunoreactivity significantly correlated with an unfavourable clinical course in papillary carcinomas of the thyroid gland. The findings of the present study obtained from surgical specimens of 39 tumours suggest that Leu-M1 immunostaining also provides significant prognostic information in patients with medullary carcinoma (MC) of this organ. Irrespective of other morphological and clinical features, local recurrences occurred 2.9 times (P less than 0.005) and death resulting from tumour occurred 4.3 times (P less than 0.03) more frequently among MCs with marked Leu-M1 positivity (greater than 15% tumour cells positively stained) in comparison to tumours with only slight or absent immunoreactivity. A significantly higher recurrence rate of intense Leu-M1-positive MCs was even evident when comparing only tumours of stage pT1-3N0M0 (P less than 0.005). Our findings infer that Leu-M1 immunostaining might be of clinical relevance to the selection of different aggressive adjuvant therapeutic procedures to be used in MCs with high or low malignant potential.

[Emergency surgical indications in chest injuries]. / Dringliche Operationsindikation beim Thoraxtrauma.

Urgent surgical intervention is required by ten to twelve per cent of all patients with thorax injuries. The author's figures were 2.3 per cent of all his 5,518 patients or 16 per cent of the severe cases among them. Immediate surgical action has proved to be necessary to cope with massive bleeding, bronchus injuries, open pneumothorax, cardiac tamponade, aortic rupture as well as with injuries of the diaphragm and oesophagus. Prognoses are good in many cases, even with considerable loss of blood. Lethality figures, depending on age and accompanying injuries, were between ten and 15 per cent for blunt injuries or something between three and five per cent for penetrating injuries.

Increased thyrotropin binding in hyperfunctioning thyroid nodules.

The object of this study was to investigate TSH receptors in hyperfunctioning thyroid nodules (HFN). In HFN, obtained from seven patients, 125-I-TSH binding as determined by equilibrium binding analysis on particulate membrane preparations, was found to be significantly increased as compared with normal thyroid tissues (five patients; P less than 0.001). Scatchard analysis of TSH-binding revealed two kinds of binding sites for both normal thyroid tissue and HFN, and displayed significantly increased association constants of high- and low-affinity binding sites in HFN (Ka = 11.75 +/- 6.8 10(9) M-1, P less than 0.001 and Ka = 2.1 +/- 1.0 10(7) M-1, P less than 0.025; x +/- SEM) as compared with normal thyroid tissue (Ka = 0.25 +/- 0.06 10(9) M-1, Ka = 0.14 +/- 0.03 10(7) M-1; x +/- SEM). The capacity of the high-affinity binding sites in HFN was found to be decreased (1.8 +/- 1.1 pmol/mg protein, x +/- SEM) in comparison with normal thyroid tissue (4.26 +/- 1.27 pmol/mg protein; x +/- SEM). TSH-receptor autoradiography applied to cryostatic tissue sections confirmed increased TSH binding of the follicular epithelium in HFN. These data suggest that an increased affinity of TSH-receptor sites in HFN in iodine deficient areas may be an important event in thyroid autonomy.

[Tumors of the anterior mediastinum--surgical treatment and prognosis]. / Tumoren des vorderen Mediastinums--chirurgische Behandlung und Prognose.

This paper reports on 96 mediastinal tumors situated exclusively or mainly in the anterior mediastinum. Early surgical intervention is always indicated to establish the diagnosis and to ensure as radical a tumor resection as possible. The surgical approach depends on the tumor size and localization and is made either by sternotomy or thoracotomy. The prognosis depends on the histological classification of the tumors: out of 30 patients with lymphomas, 19 survived as compared to 10 out of 21 patients with thymoma and 15 out of 18 patients with mesenchymal tumors. Of 16 patients with endothoracic and retrosternal goiters, none died of a cause connected with the goiter and nine out of 11 patients with mesodermal tumors survived. The indication for surgery should be established extensively, since one third of the tumors is malignant and the surgical lethality (1.8%) is very low.